The end-label/specific partial cleavage principle is widely used to sequence bases and interactions in nucleic acids. When this procedure is used on double-stranded DNA, one cuts it with a restriction enzyme, labels both ends of double-stranded segments with 32P, cuts each ith another restriction enzyme, isolates a single-end-labeled end-piece, partially breaks that with a DNA labilizing agent which is group-, base-, or sequence-specific, separates the fragments, and then visualizes those which are end-labeled by autoradiography. The positions of bands on the film reveal the exact positions of all strand breaks with respect to one another and to the original, 32P-labeled end. This basic linear structure-mapping strategy has been used to sequence bases in DNA and RNA, evaluate secondary structure, order restriction fragments, identify binding and cleavage sites, and map interactions of control proteins with regulatory sequences. In the investigations proposed here, I would like to sustain my contributions in this area by accomplishing four things: One, improve the efficiency, base-specificity, and range of the chemical DNA sequencing method and, as a consequence, the analogous chemical and enzymatic RNA sequencing methods. Two, devise a chemical procedure for cleaving DNA and RNA at single unpaired bases, for use in mapping mutations, base-base interactions, and sequence divergence in related genes. Three, increase the repertoire of chemical probes for mapping contacts between proteins and base atoms and substituents in nucleic acids. And four, probe gene regulatory elements in living cells.